title: Exploring the uncertainties of early detection results: model-based interpretation of mayo lung project.
abstract: BACKGROUND
  The Mayo Lung Project (MLP), a randomized controlled clinical trial of lung cancer screening conducted between 1971 and 1986 among male smokers aged 45 or above, demonstrated an increase in lung cancer survival since the time of diagnosis, but no reduction in lung cancer mortality. Whether this result necessarily indicates a lack of mortality benefit for screening remains controversial. A number of hypotheses have been proposed to explain the observed outcome, including over-diagnosis, screening sensitivity, and population heterogeneity (initial difference in lung cancer risks between the two trial arms). This study is intended to provide model-based testing for some of these important arguments.
  
  
  METHODS
  Using a micro-simulation model, the MISCAN-lung model, we explore the possible influence of screening sensitivity, systematic error, over-diagnosis and population heterogeneity.
  
  
  RESULTS
  Calibrating screening sensitivity, systematic error, or over-diagnosis does not noticeably improve the fit of the model, whereas calibrating population heterogeneity helps the model predict lung cancer incidence better.
  
  
  CONCLUSIONS
  Our conclusion is that the hypothesized imperfection in screening sensitivity, systematic error, and over-diagnosis do not in themselves explain the observed trial results. Model fit improvement achieved by accounting for population heterogeneity suggests a higher risk of cancer incidence in the intervention group as compared with the control group.
authors.affiliation: Department of Health Services, 650 Charles E, Young Drive S, 61-253 CHS, Los Angeles, CA 90095, USA. lushi.pku@gmail.com
authors.forename: Lu
authors.initials: L
authors.lastname: Shi
authors.forename: Haijun
authors.initials: H
authors.lastname: Tian
authors.forename: William J
authors.initials: WJ
authors.lastname: McCarthy
authors.forename: Barbara
authors.initials: B
authors.lastname: Berman
authors.forename: Shinyi
authors.initials: S
authors.lastname: Wu
authors.forename: Rob
authors.initials: R
authors.lastname: Boer
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000453:epidemiology; D000077192:Adenocarcinoma of Lung; D000368:Aged; D000369:Aged, 80 and over; D003627:Data Interpretation, Statistical; D003661:Decision Support Techniques; D055088:Early Detection of Cancer / Q000379:methods / Q000592:standards* / Q000706:statistics & numerical data; D006761:Hospitals; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000453:epidemiology; D008297:Male; D008403:Mass Screening / Q000379:methods / Q000592:standards / Q000706:statistics & numerical data; D008875:Middle Aged; D035501:Uncertainty